PI Perspective #27

April 1999     View PDF     En español

IL-2: Flushing the Reservoir?

The previous issue PI Perspective reported preliminary results of a study conducted at the National Institutes of Health (NIH). The initial findings suggested that IL-2 therapy, used in conjunction with potent anti-HIV therapy, might enhance control and elimination of HIV from certain reservoirs where the virus is known to be preserved in the body (See PI Perspective #26, IL-2: A Path Toward Functional Eradication?). At the Chicago meeting, the researchers reported that two of the volunteers have now stopped their use of anti-HIV medications with no rebound in HIV levels after being off therapy for the first three weeks. Researchers will continue to follow these patients to see when and whether HIV replication again becomes detectable. A few other studies presented at the conference did not support the findings observed in the NIH study. Since all of these studies are using somewhat different methods, it is difficult to compare their results. Larger studies are underway which may shed further light on this subject.

One study included people with a mean CD4+ count of 487 at study entry, who received a four-drug anti-HIV therapy regimen (including two protease inhibitors) with or without IL-2 therapy. The goal of the study was to see if adding IL-2 to aggressive anti-HIV therapy will further decrease evidence of HIV infection in deep tissue reservoirs, such as the lymph nodes. Four women and 52 men were included. Lymph node biopsies were performed before initiation of anti-HIV therapy, and again after patients had sustained HIV levels below the limit of detection on the most sensitive test (Roche Ultrasenstive) for greater than six months. Levels of HIV detected in the lymph nodes were similar in both those receiving anti-HIV therapy alone and those receiving anti-HIV therapy and IL-2. After a mean of 150 days after starting anti-HIV therapy, this study showed similar rates of decline of cell-bound HIV in the lymph nodes between the two groups. This suggests that, in this combination, IL-2 did not have an impact on accelerating HIV clearance from reservoirs of HIV infection. However, this study used a somewhat different method of measuring the effect of IL-2 on reservoirs of infection. While based on results from only a small number of people, there was information suggesting that fewer people receiving IL-2 showed evidence of persistent virus production, however.

Another study included only three people, and included a more aggressive eradication approach, combining anti-HIV therapy with IL-2 and a potent but highly toxic immune activator, OKT3. The rationale behind this approach is to see if using IL-2 and OKT3 to activate immune cells, HIV hidden quietly in cells will be forced into view of both anti-HIV drugs as well as anti-HIV responses of the immune system. While there was clearly evidence that IL-2 and OKT3 were activating the immune system, the combined toxic effects of the therapies, particularly the side effects of OKT3, overwhelm any potential benefits of this therapeutic approach. Side effects include severe fevers and rigors. One volunteer experienced temporary kidney (renal) failure.